JP5296984B2 - Cosmetic or dermatological composition for inhibiting skin aging phenomenon - Google Patents

Description

  The present invention relates to a novel peptide derivative and a topical cosmetic or dermopharmaceutical composition containing the peptide derivative, and a method of using the composition for the purpose of preventing skin aging and forming scars on the skin. Peptide derivatives that are fragments of elastin are used alone or in combination with other active ingredients in a cosmetically acceptable medium.

  Skin is a high percentage of the individual image. The skin condition has always been a concern for people. In recent years, research in the field of skin physiology has progressed, and cosmetics that deal with various functional disorders caused by external stress and aging have been provided. However, many problems that cannot be fully understood remain.

  Examples include general skin aging phenomena that appear in wrinkles, dry skin, rough skin, thinning and sagging of the skin. Countermeasures for the aging phenomenon are important issues in research in the field of skin physiology and in the cosmetic industry.

  The occurrence of the aging phenomenon is caused by external or internal factors. When proteolysis induced by solar radiation decreases due to a decrease in the ability to produce collagen and the macromolecules that make up connective tissue, the skin dries, loses elasticity, and thins.

  A number of cosmetic compositions have been provided so far to improve the skin condition of the face. Examples include moisturizing products, anti-wrinkle creams, and lotions that calm and smooth the skin. However, these products may have problems with side effects and quality stability, and the expected effects may be lost over time. Such problems are particularly common in products containing vitamins and herbal ingredients.

  The present invention aims to solve cosmetic problems and related technical problems caused by such a phenomenon.

An object of the present invention also relates to novel particularly intended for cosmetic or dermopharmaceutical composition for the skin care facial portion includes containing a peptide derivative having a structure of Formula I below in a cosmetically acceptable medium The object is to provide a cosmetic or dermatological composition.

  It is another object of the present invention to provide a method for using and producing a cosmetic or dermopharmaceutical composition for skin care and scalp care, particularly for suppressing aging and promoting skin scar formation.

  Another object of the present invention is to provide a skin cosmetic treatment method that suppresses aging such as wrinkles. More particularly, the composition according to the invention is applied to the relevant sites in an effective amount. Other features, aspects and advantages of the present invention are described below.

  There have already been reports on the use of some peptides and their derivatives in cosmetics. K. Lintner and O. Peschard, “Biologically active peptides”, Int. J. Cosm. Sci. 22,207-218, 2000 is an example.

  In the present invention, it has been found that a cosmetic composition containing a peptide derivative having the general oligopeptide general structure of the following formula I has a skin aging phenomenon suppressing effect superior to those reported so far. .

The present invention is directed to compounds having the structure of Formula I.
A compound having the formula I: Pal-Val-Gly-Val-Ala-Pro-Gly (SEQ ID NO: 6) for tightening skin and / or improving wrinkles.

  When the novel compound according to the present invention is used in a cosmetic or dermatological composition, it has a cosmetic effect, and is further strengthened by using other active ingredients in combination. Regardless of the presence or absence of synergistic effects, wrinkles are reduced, the skin moisturizing function is improved, the skin is tightened, and the skin becomes fine. No existing cosmetic composition has the same advantages as the present invention.

  Ceramide is an important lipid molecule in the skin epidermis. Ceramides are also well known compounds for use in skin care products. It has been confirmed that when ceramide is used in combination with a peptide and / or a peptide derivative, it exhibits a wrinkle reducing effect superior to a cosmetic composition containing only a peptide due to a synergistic effect. Ceramide is usually used to treat dry and cracked skin. It is a noteworthy result that ceramide has been confirmed to be effective in cosmetic treatment.

  The peptide Val-Gly-Val-Ala-Pro-Gly is known as a fragment of the protein elastin. It is the most frequent sequence within the protein. The chemotactic movement (the property of attracting fibroblasts to the site of inflammation or scar) has already been reported (see Senior and al. J. Cell Biol. 99, 870-874, 1984). Since derivatization of the peptide results in a structure with higher lipophilicity, the peptide derivative has a markedly improved penetration into the skin, and exhibits a cosmetic effect that requires penetration of the peptide derivative into living skin tissue. During the development of the present invention, among the same peptides, the following derivative: Palmitoyl-Val-Gly-Val-Ala-Pro-Gly-OH (SEQ ID NO: 6) (or Pal-Val-Gly-Val-Ala-Pro- Gly-OH, Pal-val-Gly-Val-Ala-Pro-Gly, and Pal-VGVAPG) have the effect of restoring the skin of the neck and face and regenerating the skin. It was discovered to have a cosmetic effect. This regeneration effect also improves the skin moisturizing effect.

  The properties of the peptide derivatives according to the invention produce a further synergistic effect in combination with ceramide. Ceramide belongs to complex lipids and is found in the upper layer of the skin epidermis. (See Wertz and al., J. Invest. Dermatol. 84, 410-412, 1985.) Ceramides particularly preferred in the Wertz literature are ceramides 1, 3, and 4-7. These ceramides have the following general formula A:

式Ａの基礎構造は、式Ｂの如く改変され、誘導される。セラミドＮ‐アシル‐Ｄ‐エリスロ‐スフィンゴシン（Ｎ‐Acyl‐D‐erythro‐sphinegosine）は、哺乳類のグリコ脂質、リン脂質、スフィンゴミエリンの構造要素である。他の好ましいとされるセラミドとして、トリヒドロキシパルミタミドヒドロキシプロピルミリスチル・エーテル（trihydroxypalmitamidohydroxypropylmyristyl ether）、ｎ‐ステアロイル‐ジヒドロスフィンゴシン（n‐stearoyl‐dihydrosphingosine）及びパルミタミド・ミリスチル・セリナート（palmitamido myristyl serinate）である。本発明に基づくその他の有用なセラミドとしては、前述の構造（式Ａ）のセラミドで、同構造内のアシル基Ｒ⁶（式Ｂ内では‐(ＣＨ_２)_１６ＣＨ_３基として表示）は、炭素数１４から２２の脂肪酸鎖である。式Ａ内のＲ^７は同一でも異なっても良いが、炭素数１４から２２の脂肪酸鎖である。脂肪鎖は飽和でも不飽和でも、置換体であってもなくても、直鎖状でも分枝状でも良い。尚、炭素数１０以下のＲ^６を有するセラミドは好ましくない。

The basic structure of Formula A is modified and derived as in Formula B. Ceramide N-acyl-D-erythro-sphinegosine is a structural element of mammalian glycolipids, phospholipids, and sphingomyelin. Other preferred ceramides are trihydroxypalmitamidohydroxypropylmyristyl ether, n-stearoyl-dihydrosphingosine and palmitamido myristyl serinate . Other useful ceramides according to the present invention are the ceramides of the aforementioned structure (formula A), wherein the acyl group R ⁶ (shown as-(CH ₂ ) ₁₆ CH ₃ group in formula B) is: It is a fatty acid chain having 14 to 22 carbon atoms. R ⁷ in formula A may be the same or different, but is a fatty acid chain having 14 to 22 carbon atoms. The fatty chain may be saturated or unsaturated, may or may not be substituted, and may be linear or branched. Note that ceramide having R ⁶ having 10 or less carbon atoms is not preferable.

  Many studies have been conducted to obtain these components by means of extraction, synthesis, etc. and use them in cosmetics. Ceramide strengthens the skin membrane and has the function of adjusting the water flow rate through the stratum corneum. (See, for example, Lintner and al. Int. J. Cosmet. Sci 19, 15-25, 1997). It has been clarified that when a peptide and ceramide are used in combination for a cosmetic or dermatological composition, the anti-aging effect of the peptide of the present invention can be greatly improved and the aging phenomenon can be remarkably suppressed. In particular, these cosmetic compositions can be used for wrinkle removal and wrinkle prevention. That is, the novel peptide and / or peptide derivative has a certain aging phenomenon countermeasure effect that can be objectively measured when used in combination with ceramide. In order to improve the skin condition, the cosmetic effect is enhanced, such as stimulating or suppressing biochemical processes to improve the wrinkle reduction effect. The ceramide is mixed in an amount suitable for improving the anti-aging effect of the peptide and / or peptide derivative.

  In practicing the subject matter of the present invention, a suitable useful compound is formulated in a cosmetic or dermatological composition, and an appropriate amount is applied to the relevant part of the face for 2 weeks up to 2 months.

  Peptides and peptide derivatives of elastin fragments can be synthesized by conventional chemical synthesis (heterogeneous or homogeneous reaction) or chemical synthesis of enzymatic reactions with essential amino acids or their derivatives (Kullman and al., J. Biol. Chem. 255). 8234, 1980).

In order to improve the biochemical utility and skin penetration of the peptide, esterification of a carboxyl group with a linear or branched, saturated or unsaturated, alcohol with or without a hydroxy group reaction by, ^{R 2} is 1 to 24 carbon atoms, preferably to produce a compound H-X-Y-oR ² is an alkyl chain of 1 to 3 or 14 to 18 carbon atoms. Alternatively, a compound H—X—Y—NR ³ R in which R ³ and R ⁴ are independently of each other and are H or an alkyl chain having 1 to 12 carbon atoms, preferably 1 to 3 carbon atoms, by an amidation reaction using an amine. ⁴ to generate, raise the lipophilicity of the same peptide.

Peptide derivatives, acyl derivatives, such as acetic acid, caproic acid, lauric acid, myristic acid, octanoic acid, palmitic acid, stearic acid, behenic acid, linoleic acid, linolenic acid, oleic acid, Izosutearin acid, elaidic acid, 2- Including derivatives of ethylhexanoic acid, fatty acids of coconut oil, fatty acids of palm oil, lanolin fatty acids and the like. As the acyl group, for example, an acetyl group, a palmitoyl group, an eridoyl group, a myristyl group, a biotinyl group, and an octanoyl group are preferable.

  Peptides and peptide derivatives can be obtained by chemical synthesis. It can also be produced by culturing bacterial strains that have been modified (or not modified) by genetic engineering for the purpose of generating the desired sequence or another fragment.

The peptide can also be obtained by extracting animal or plant proteins having the desired sequence in the structure, followed by controlled hydrolysis, with or without enzymatic reaction: (AA) _n − It can also be obtained by dissociating peptide fragments of n = 0 to 3 with Val-Gly-Val-Ala-Pro-Gly (SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4).

  Although not required, in order to practice the present invention, it is also possible to extract the relevant protein and then hydrolyze it, or hydrolyze the crude extract and then purify the peptide. It is also possible to use the hydrolysis product without extracting the relevant peptide. However, it should be noted that the enzymatic reaction of hydrolysis is stopped without delay, and the content of related peptides is measured by an appropriate analytical means (radioactivity trace, fluorescent antibody method using a specific antibody, precipitation antibody method, etc.).

  If you are an expert in protein and peptide extraction and purification work, you can easily devise a method for obtaining inexpensive and high-purity products.

  The following peptides constitute an unrestricted selection list of peptide analogs having 6 or more amino acids. Eladoyl-Val-Gly-Val-Ala-Pro-Gly (SEQ ID NO: 19), Palmitoyl-Ala-Val-Gly-Val-Ala-Pro-Gly (SEQ ID NO: 20), Acetyl-Ile-Ala-Val- Gly-Val-Ala-Pro-Gly (SEQ ID NO: 21). A preferred combination contains the peptide N-acyl-Val-Gly-Val-Ala-Pro-Gly (SEQ ID NO: 4). A particularly preferred combination contains palmitoyl-Val-Gly-Val-Ala-Pro-Gly (SEQ ID NO: 6).

  The aforementioned peptide fragment of elastin or a derivative thereof is incorporated in the cosmetic composition according to the present invention. The concentration of the peptide fragment of elastin or a derivative thereof is 0.00001% by weight to 10% by weight, particularly preferably 0.0001% by weight to 1% by weight. (Wt% is the weight concentration relative to the total weight of the composition.) A concentration range of 0.001% to 5% by weight is also useful, preferably about 1 ppm to 500 ppm.

The implementation of the invention, cosmetic or dermopharmaceutical composition, peptide compound or peptide derivative of the formula I and those containing at least one ceramide.

  The combination of peptide and ceramide according to the present invention, when using one or more ceramides, the total concentration of ceramide is in the range of 0.0001% to 10% by weight, preferably in the range of 0.001% to 1% by weight. Is needed. Further, the peptide concentration is preferably about 100 to 400 ppm, and the ceramide concentration is preferably about 1 to 8% by weight.

When one ceramide is used, R ¹ of the peptide is preferably an acyl group such as a palmitoyl group, and R ² is preferably a hydrogen atom (H).

  The invention relates to the formulation of the peptides according to the invention with any ceramide. When the ceramide is added to one or a plurality of peptides or peptide analogs or peptide derivatives described in the present case, the skin aging phenomenon suppressing effect such as wrinkle countermeasures is exhibited. In particular, N-acyl-sphingosine and N-acyl-dihydrosphingosine, also known as N-acyl-sphinganine, and analogs and derivatives thereof It is effective when an appropriate amount of ceramide based on the above is blended. Further, N-srearoyl-sphinganine is more preferable.

In an embodiment of the present invention, as a cosmetic composition, a peptide, palmitoyl-Val-Gly-Val-Ala-Pro-GlyOH (SEQ ID NO: 6) is added in a concentration range of 0.0001 wt% to 0.01 wt%. contains. N-stearoyl-dihydrosphingosine (N-stearoyl-
dihydrosphingosine) in a concentration range of 0.001% to 10.0% by weight. Another effective concentration range is 0.001% to 5% by weight of peptide and 0.01% to 1.0% by weight of ceramide. In an embodiment of the present invention, the amount of hexapeptide is 0.002% by weight and the amount of ceramide 2 is 4% by weight. The above blending is preferably carried out on an oil basis.

  Commercially available hexapeptide-containing compositions include “BIOBUSTYL” and “BIOPEPTIDE EL”, which are available from SEDERMA, France. The product contains 10 to 500 ppm of palmitoyl-Val-Gly-Val-Ala-Pro-Gly (SEQ ID NO: 6) and other ingredients as additive substances. DERMAXYL (registered trademark) is a product available before the publication of this case, about 200 ppm by weight (0.002% by weight) of Pal-Val-Gly-Val-Ala-Pro-Gly (SEQ ID NO: 6), and about 4% by weight of ceramide 2 is contained in the base oil. Ceramide 2 is commercialized under the name “CERAMIDE 2”. “CERAMIDE 2” is composed of 100% N-stearoylsphinganine, also known as N-stearoyl-dihydrosphingosine. These compositions are used for the purpose of preparing the compositions according to the invention.

  Other ceramides and other peptide derivatives having the aforementioned common sequence (formula I) are preferably utilized within the scope of the present invention.

  Preferred embodiments of the present invention include, in particular, the combination of peptides and peptide derivatives according to the present invention with other cosmetic active ingredients (see below).

How to use the peptides according to the invention is formulated with one or more ceramides, the skin care for the purpose of eliminating temporary or long-term noticeable wrinkles are effective. A preferred composition for that purpose is a wrinkle prevention product that is applied topically (skin, especially the face and hands). Peptides of the present description may be utilized by incorporating ceramide shampoo, conditioner, a cleaner or the like. The peptide can also be used in conventional anti-wrinkle products to improve the anti-wrinkle effect of conventional products. This peptide also serves as a basis for the effect of combating wrinkles. Since the mixture of the peptide and ceramide has various desirable properties, it can be used for shampoos, conditioners, UV prevention products, hair gels, and other products described later, even though wrinkle countermeasures are not involved at all.

  Matrikines are peptide fragments. Matricaine sequences are usually composed of 20 or fewer amino acids and are generated from matrix proteases when disinfecting skin wounds prior to scar formation.

  The hexapeptide VGVAPG generated during elastin hydrolysis by elastase is a kind of Matricaine. The hexapeptide VGVAPG regenerates a very useful connective tissue during skin scar formation and allows a retroactive effect on the process of cell proliferation.

  The process of scar formation requires many types of cells. Granulocytes, mast cells, endothelial cells, platelets, keratinocytes, fibroblasts and monocytes. All of these cells are not necessarily in the damaged area of the same region, and need to be adjusted to reach the wound site of the cells simultaneously. The signal transduction mechanism to the cell is called chemotaxis. A chemical signal collects the target cell at a site that requires its presence. Cells identify chemotactic molecules and move physically according to a concentration gradient. There are several types of chemotactic molecules such as cytokin, short sequence peptide, TNF-α and the like.

  Palmitoyl-VGVAPG (SEQ ID NO: 6) has the properties of Matricaine. Its properties are chemotaxis, cell growth and calcium mobilization, matrix reorganization through the regulation of metalloproteases. These properties are applied to cosmetic effects that suppress the aging phenomenon, and are used to regenerate the dermis that is finer and more elastic.

Thus, it has been discovered that certain compounds of formula I are chemotactic. Accordingly, the present invention is also directed to a method of using a cosmetic or dermopharmaceutical compound (composition) comprising at least one compound of formula I for promoting skin scar formation, dermal regeneration. More specifically, it is directed to a method of using at least one compound having chemotaxis of Formula I, or a method of using a cosmetic or dermopharmaceutical composition containing said compound. The compound used for the purpose of promoting skin scar formation may be a compound of formula I wherein R ^{1 of} formula I is a palmitoyl group.

  For example, in the formulation according to the present invention, the effect of the peptide derivative: Pal-VGVAPG (Elastin Matricaine) (SEQ ID NO: 6) can be enhanced by adding ceramide containing a large amount of natural components. The ceramide added is ceramide 2. Ceramide 2 has a moisturizing action and an action to bind and regenerate the epidermis, and has a secondary function of protecting keranosite. These actions complement each other, and the effect appears in the epidermis. The effect that appears in the epidermis is complemented by the effect of reorganizing the dermis. The effect of reorganizing the dermis is due to the chemotaxis and proliferation of fibroblasts for matrix tissue reorganization.

  Examples of the composition according to the present invention include the following. Emollient lotion (or emulsion or cream), skin care or hair care emulsion (or cream), cleansing lotion (or emulsion), foundation base, sunscreen lotion (or emulsion or cream), self-tanning lotion (or emulsion or cream), wrinkles Shaving cream (or mousse), after-shave lotion, shampoo, lipstick, mascara or nail polish.

  These compositions can also be used as lipstick and rough lip prevention lip balm sticks or eye makeup cosmetics and facial foundations or cheeks.

  When the composition according to the present invention is a water-in-oil emulsion or an oil-in-water emulsion, the oil phase needs to be composed of a mixture in which at least one oil is blended with an oil obtained by extraction or synthesis. Since fats and oils are blended, the result is another fat and oil. The oil phase of the emulsion constitutes 5-60% of the total weight of the emulsion.

  The aqueous phase of the emulsion preferably constitutes 30 to 85% of the total weight of the emulsion. The emulsifier can be blended in a proportion within the range of 1 to 20%, preferably 2 to 12% of the total weight of the emulsion. When the composition according to the present invention is an oily lotion of an oily alcohol or an aqueous alcohol, it can constitute a sunscreen lotion including an ultraviolet absorption filter, a soft skin lotion or the like. In addition, the oil lotion can constitute an oil foam containing an oil-soluble surfactant, bath oil, or the like.

The main additive substances that can be incorporated into the composition according to the present invention are as follows. Organic solvent or hydroglycol solvent containing MP diol and polyglycerin, oil or fat by extraction or synthesis, ionic or nonionic thickener, softener, turbidity agent, stabilizer, softener, silicon, α or β hydroxy acid, Non-foaming agents, humectants, vitamins, fragrances, preservatives, chelating agents, colorants, gelling and thickening polymers, surfactants and emulsifiers, other water-soluble or oil-soluble active ingredients, plant extracts, tissue extracts, Examples include marine extracts, UV filters, and antioxidants.

  Particularly preferred monohydric or polyhydric alcohols are selected from ethanol, isopropanol, propylene glycol, glycerol and sorbitol.

  Examples of the fats and oils include mineral oil petrolatum oil. Animal oils include whale oil, shark oil, fur seal oil, herring oil, halibut liver oil, cod oil, tuna oil, turtle oil, cow leg oil, horse leg oil, sheep leg oil, mink oil, otter oil, marmot Oil etc. are mentioned. Vegetable oils include almond oil, wheat germ oil, jojoba oil, sesame oil, sunflower oil, palm oil, walnut oil, shea butter, shorea fat, macadamia nut oil, black currant seed oil and the like.

  Examples of fatty acid esters include esters of saturated or unsaturated acids having 12 to 22 carbon atoms, esters of lower alcohols such as isopropanol and glycerol, linear fatty alcohols, molecular fatty alcohols, saturated fatty alcohols, unsaturated fats. Examples thereof include esters of fatty alcohols having 8 to 22 carbon atoms selected from the group consisting of alcohols and esters of 1,2-alkanediols having 10 to 22 carbon atoms.

  As oils and fats, petrolatum, paraffin, lanolin, hydrogenated lanolin, tallow, acetylated lanolin, and silicone oil can be blended.

  Wax wax, lanolin wax, beeswax, candelilla wax, microcrystalline wax, carnauba wax, whale wax, cacao butter, shea butter, silicon wax, hydrogenated crude oil at 25 ° C, sucrose glyceride, oleic acid And calcium and magnesium salts and aluminum salts of myristic acid, linolenic acid and stearic acid.

  Examples of fatty alcohols include lauryl alcohol, cetyl alcohol, myristyl alcohol, stearyl alcohol, palmityl alcohol, oleyl alcohol, and 2-decyltetradecanol or 2-hexyldecanol. Of Gerve alcohol. In the emulsifier, as polyoxyethylenated fatty alcohol, lauryl alcohol and cetyl alcohol and stearyl alcohol and oleyl alcohol having 2 to 20 mol of ethylene oxide molecule, alkyl ether of glycerol, and having 12 to 20 carbon atoms having glycerol molecule as 2 to 20 mol 18 alcohols are mentioned. Use of cellulose derivatives, polyacrylic acid derivatives, guar gum, locust bean gum, xanthan gum or the like as a thickener is also useful.

  Compositions according to the present invention also include cosmetics and dermatological additives, especially moisturizing products, softeners, skin disease treatment products, UV filters, bactericides, colorants, preservatives, perfumes and aerosol gases. It can be blended.

  When the composition according to the present invention is a dispersion, it is an aqueous dispersion of lecithin using a surfactant, or spherules lipidiques composed of an organized molecular layer containing an encapsulated aqueous phase. It is an aqueous dispersion. The lipid compound for that purpose is as follows. Long chain alcohols and long chain diols, sterols such as cholesterol, phospholipids, sulfuric acid and cholesteryl phosphate, long chain amines and quaternary ammonium derivatives of long chain amines, dihydroxyamines, polyoxyethylenated fatty amines, esters of long chain amino alcohols A salt of the same ester and a quaternary ammonium derivative, a fatty alcohol phosphate such as dicetyl phosphoric acid or its sodium salt, an alkyl sulfuric acid such as sodium cetyl sulfate, a salt of a fatty acid, or French Patent Nos. 2315991, 1477048, Examples thereof include lipids described in No. 2091516, International Patent Application Nos. WO83 / 01571, and WO92 / 08855.

  As other lipids, lipids containing a long-chain lipophilic moiety having 12 to 30 carbon atoms, which are saturated or unsaturated, branched or linear, can be used. Examples include oleyl chain, lanolyl chain, tetradecyl chain, hexadecyl chain, isostearyl chain, lauryl chain, alkylphenyl chain, and the like. The hydrophilic group of the lipid can be both an ionic group and a nonionic group. Nonionic groups include groups of polyethylene glycol derivatives. Further, as the lipid constituting the thin layer structure, polyglycerol ethers described in French Patent Nos. 1477048, 2091516, 2465780, and 2482128 can be advantageously used.

  As the ionic group, amphoteric (or anionic or cationic) compound derivative groups can be advantageously used.

  Other lipids that can be used for vesicle formation as described in International Patent Application WO 83/01571 are glycolipids such as lactosylceramide, galactocerebroside, ganglioside, trihexosylceramide, phosphatidylglycerol, phosphatidylinositol Such as phospholipids.

  In addition to the peptides and / or peptide derivatives and ceramides described herein, the composition according to the present invention contains active additives commonly used in cosmetics, personal care products, topical (transdermal) drugs. One or more may be contained.

  Active substances that can be combined with peptides, peptide derivatives and ceramides are substances having a pharmacological effect, a food effect, or a substance having an appropriate cosmetic effect. If the active substance is water-soluble, it is dissolved homogeneously or contained in the aqueous phase within the vesicle. Water-soluble substances having cosmetic and / or pharmacological effects are products for skin and hair care and treatment. For example, humectants include glycerin, sorbitol, pentaerythritol, pyrrolidonic acid and its salts. Examples of self-tanning agents include y-dialdehydes such as dihydroxyacetone, erythrulose, glyceraldehyde, and tartaraldehyde, and these compounds may be combined with a colorant. Furthermore, water-soluble UV filters, antiperspirants (body odor prevention agents, astringents, refreshing agents, tonics, scar-forming agents, keratolytic agents, hair removal agents, perfumes), plant tissue extracts such as polysaccharides, water-soluble coloring agents Oxidants such as anti-dandruff agents, sebum secretion inhibitors, decolorizers such as hydrogen peroxide, and reducing agents such as thioglycolic acid and its salts.

  Similarly, vitamins B1 to B12, C, D, H, K and derivatives thereof, peptides hormones, steroid hormones, enzymes such as superoxide dismutase, vaccines, steroidal or nonsteroidal anti-inflammatory agents such as hydrocortisone, antibiotics Also included are antibacterial and fungicides, cytotoxic agents or antitumor agents.

  If the active substances are oil-soluble, these substances are included in the oil phase of the emulsion or in the layer of vesicles such as liposomes, micelles, chylomicrons. Oil-soluble active substances include oil-soluble UV filters, substances intended to improve dry or aging skin, tocopherol, vitamin E, F or A and esters thereof, retinoic acid, antioxidants, essential fatty acids, glycyrrhetinic acid, keratin It is selected from the group consisting of solubilizers and carotenoids, ceramides and pseudoceramides, or any complex lipid that is isomorphic to the natural ceramide of the skin.

  The peptides of the present invention are selected from the group consisting of solutions, dispersions, emulsions, pastes, and powders, either added alone to the cosmetic composition according to the present invention or mixed in advance with an appropriate binder. It can be used in a state where The peptide may be used alone or in combination with other active ingredients described in this case (may be ingredients not described) to produce macrocapsules, microcapsules, nanocapsules, liposomes, chylomicrons, macros It is transmitted by a carrier selected from the group consisting of particles, microparticles, nanoparticles and microsponges. These peptides are also adsorbed by powdered organic polymers, talc, bentonite and other inorganic media.

  The peptide is attached to the fiber in any shape (a shape of macroparticle, microparticle, nanoparticle, macrocapsule, microcapsule, nanocapsule connected (or mixed, adsorbed)), and the contact between the fiber and the skin The beauty effect is exerted continuously through the surface. Specifically, processing can be performed on all materials such as tights, underwear, handkerchiefs, wet tissues, etc., such as daywear or nightwear clothes / underwear synthetic fibers, natural fibers, wool, etc. that are in direct contact with the skin.

As examples of the present invention, some representative cosmetic compositions are introduced, but the scope of the present invention is not limited thereto.
Example 1 Gel g / 100g
Carbomer 0.3
Propylene glycol 2.0
Glycerin 1.0
White petrolatum 1.5
Cyclomethicone 6.0
Crodacol C90 0.5
Lubrajel MS 10
Trietanoramine 0.3
Palmitoyl-Val-Gly-Val-Ala-Pro-Gly-OH (SEQ ID NO: 6) 0.0005
Water, preservative, fragrance

  This gel is prepared by dissolving the peptide in 80 ° C water, mixing the other components at 80 ° C, adding each phase one at a time and cooling to 30 ° C, then adding lybragel, preservative and flavor. .

  This gel obtained with a simple formulation can be used as a daily face care, in particular to eliminate swelling around the eyes.

Example 2 Anti-wrinkle cream g / 100g
Deionized water to 100 appropriate amount Carbomer 0.10
Potassium sorbate 0.10
Transcutol 3.00
(Diethylene glycol monoethyl ether)
Glycerin Croda 8.00
Volpo S2 "Stealess 2" Croda 0.60
Kurodafos CES "Cetearyl alcohol (and) dicetyl phosphate (and) ceteth-10 phosphate" Croda 4.00
DC 344 “Cyclomethicone” DowCorning 2.00
Crodamole GTCC “Caprylic / Capric Triglyceride” Croda 10.00
Kuryl 3 "Sorbitan stearate" Croda 1.60
Paraben 0.30
Sodium hydroxide 30% 0.35
Demineralized water 3.50
DERMAXYL Sedema 2.00

  The composition is prepared by the following method. The oily material is mixed at 70-80 ° C., the aqueous material is mixed in the same manner, and the two mixtures are mixed to make an emulsion. DERMAXYL is C12-15 Alkyl benzoate C12-15 Alkyl benzoate-Tribehenin-Ceramide 2-PEG-10 Rapeseed Sterol-Palmitoyl Oligopeptide (SEQ ID NO: 6) and is available from Sederma.

Example 3 Anti-aging sedative cream g / 100g
Deionized water vs. 100 appropriate amount Ultrez 10 “Carbomer” Noveon 0.20
Potassium sorbate 0.10
Butylene glycol 2.00
Phenova "Phenoxyethanol (and) mixed paraben"
Crodarom 0.80
Crill 3 “Sorbitan stearate” Croda 1.00
Crillet 3 “Polysorbic Acid 60” Croda 2.50
DC 200 (Dimethicone) 2.50
Crodamol TN (isotridecyl isononanoate)
Croda 5.00
Crodamol GTCC "Caprylic acid / Capric acid triglyceride"
Croda 5.00
Crodamol SS “cetyl ester” Croda 1.00
Super Heartolan “Lanoline Alcohol” Croda 0.50
Super Sterol Ester 0.30
"Fatty acid (C10-30) (cholesterol / lanosterol ester)"
Crodacol CS90 “Ceteraryl Alcohol” Croda 3.00
Demineralized water 2.50
Sodium hydroxide 38% 0.25
CALMOSENSINE
“Butylene glycol (and) water (and) laureth-3 (and)
Hydroxyethyl cellulose (and)
Acetyl dipeptide-1 cetyl ester) "
Sederma 4.00
Palmitoyl-Val-Gly-Val-Ala-Pro-Gly (SEQ ID NO: 6)
Sedera 0.001
Ceramide 2
(N-stearoyl dihydrosphingosine) Sederma 0.05

  This emulsion is prepared in a manner similar to the previous example. (The preheated and mixed oil phase is mixed with the preheated and mixed water phase. Make an emulsion and cool.)

Example 4 Anti-atrophy skin gel g / 100g
Phase A
Desalted water to 100 appropriate amount Phase B
Butylene glycol 5.00
Phenova "Phenoxyethanol (and) mixed paraben"
Crodarom 0.80
Phase C Crill 3 “Sorbitan stearate” Croda 1.20
Crillet 3 “Polysorbic acid 60” Croda 3.00
DC 200 “Dimethicone” 2.00
Crodamol IPM "Isopropyl myristate"
Croda 5.00
Crodamol W “stearyl heptanoate” Croda 0.30
Crodamol GTCC "Caprylic acid / Capric acid triglyceride"
Croda 5.00
Crodacol CS90 "Cetearyl alcohol" Croda 2.00
Ceramide 2 (N-stearoyl sphinganine)
Sederma 0.10
Phase D Carbopol 980 2% “Carbomer” 10.00
Phase E potassium sorbate 0.10
Phase F Demineralized water 2.00
Sodium hydroxide 0.20
Phase G Demineralized water 10.0
Pal-Val-Gly-Val-Ala-Pro-Gly (SEQ ID NO: 6)
Sederma 0.00015
ESCULOSIDE Sedema 0.5%

  This gel can be prepared by the following method. Homogenize Phase B and add to Phase A. Heat the (A + B) phase to 75 ° C. Heat Phase C and Phase D to 75 ° C. Add Phase C to Phase (A + B) and mix thoroughly. Then add phase D to phase (A + B + C). And after adding F phase and E phase, G phase is added at the temperature of about 35 degreeC.

  The effect by this invention is demonstrated with the following method.

Example 5 Skin tightening effect evaluation test Ten women aged 32 to 56 years old were subjects, and a test for evaluating the skin tightening effect was performed. The following compositions were used for the test.
Composition weight%
Stearic acid 3.50
Beeswax 0.50
Cetyl alcohol 1.50
Octyl palmitate 1.50
Isostearyl neopentanoate 2.50
PPG-15 stearyl ether 3.00
Cyclomethicone 4.50
Stearoxy dimethicone 2.00
Cetearyl octoate 3.00
Deionized water to 100 appropriate amount Trietanolamine 99% 1.00
Propylene glycol 3.00
Pal-Val-Gly-Val-Ala-Pro-Gly-OH (SEQ ID NO: 6) 0.0004

  Test method: The sensor of “Fermometer” (Courage & Khazaka) can suck the skin by applying a negative pressure of about 500 mbar continuously to a certain area of the skin. Rays cause a declination due to deformation of the segment and are recorded in the form of a graph, and the skin condition (parameters such as tightening, elasticity, and tension) can be obtained from the graph.

  A cream containing the peptide derivative of the present invention was applied to the forearm twice a day for one month. A placebo cream containing no peptide was similarly applied to the other forearm.

  After applying these creams for one month, changes in the skin condition of the skin to which the cream containing the peptide derivative was applied decreased in sagging and increased in tension and firmness. However, no clear change was seen in those who applied placebo cream.

Example 6 In vitro test for properties of palmitoyl-VGVAPG (SEQ ID NO: 6)
A molecular approach was selected for analysis of activated or inactivated genes when culturing the epidermis with Pal-VGVAPG (SEQ ID NO: 6). At the gene expression level, a temporal image of cellular activity can be obtained and compared with resting control cells to reveal differences in activity and suppression when responding to external conditions. DNA chip technology has made it possible to analyze 400 DNA sensors. This 400 DNA sensor can encode 400 proteins that cover the main functions of skin cells. After the peptide was inserted into the medium, a gene with an increased messenger RNA production rate was detected by the polymerase chain reaction (PCR) method.

  After the epidermis “Skin-Ethic” was cultured in an appropriate medium for 24 hours in advance, a sample treated with Pal-VGVAPG (SEQ ID NO: 6) for 4 hours and an untreated control sample (control cells) were prepared. The change in the gene of the treated sample was expressed as a ratio of the control sample. As a result, it was found that activation occurred in the following five genes from the numerical values shown.

  The most activated gene was the GCP2 gene responsible for the synthesis of chemotactic proteins involved in the attraction of wound bactericidal cells (monocytes and neutrophils). Also, the specificity of this peptide is noteworthy in that five specific genes have been activated.

Example 7 Moisturizing effect and anti-wrinkle foundation composition Weight%
Demineralized water 53.36
Potassium hydroxide 10% 1.30
Polysorbic acid 80 0.10
Titanium dioxide 6.00
Talc 3.05
Yellow iron oxide 1.80
Red iron oxide 1.00
Black iron oxide 0.15
Propylene glycol 6.00
Magnesium aluminum silicate 1.00
Sodium carboxymethylcellulose 0.12
DiPPG3 Adipic acid myristyl ether 12.00
Isostearyl neopentanoate 4.00
Crodafos CS 20 4.00
Steareth-10 2.00
Cetyl alcohol 0.50
Steareth-2 0.50
Ceramide 2 0.10
Pal-Val-Gly-Val-Ala-Pro-Gly-OH (SEQ ID NO: 6) 0.0004
Preservative appropriate amount

EXAMPLE 8 A colored cream usage test based on Wrinkle Countermeasure Example 7 was conducted, and 24 subjects (average age 54 years) were subjects. Wrinkles around the eyes were evaluated by self-assessment questionnaire and skin replica technique. The colored cream was applied to the relevant site twice daily for 56 days. Wrinkle measurements were taken on days 0 and 56. As a result, wrinkle reduction was measured by this test (see table). Moreover, the reduction of wrinkles could be observed with the naked eye. However, wrinkle reduction was not observed in the colored cream containing no peptide or ceramide.

Claims (7)

A cosmetic or dermatological composition comprising a compound and an additive,
The compound contains a peptide of formula I: Pal-Val-Gly-Val-Ala-Pro-Gly (SEQ ID NO: 6) as an active ingredient for skin tightening and / or wrinkle improvement,
The composition contains an oil-soluble active ingredient,
The oil-soluble active ingredient is ceramide,
The ceramide is N-stearoyl-dihydrosphingosine ,
A cosmetic or dermatological composition, wherein the additive is an additive that can be used as a cosmetic. A cosmetic or dermatological composition according to claim 1,
A cosmetic or dermatological composition, wherein the peptide is obtained by any means selected from the group consisting of chemical synthesis, enzymatic reaction, fermentation, or extraction from vegetable protein. A cosmetic or dermatological composition according to claim 1 or 2,
The composition, cosmetic or dermopharmaceutical composition characterized in that it contains 0.00001% to 10 wt% of the concentration of the peptide. A cosmetic or dermatological composition according to any one of claims 1 to 3,
The composition, cosmetic or dermopharmaceutical composition characterized by containing a ceramide 0.0001 wt% to 10 wt% of the concentration. A cosmetic or dermatological composition according to any one of claims 1 to 4,
The compound in the composition is in a state selected from the group consisting of a solution, a dispersion, an emulsion, a paste, and a powder, and is used alone or in a premixed state, or
Transmitted by a carrier selected from the group consisting of macrocapsules, microcapsules, nanocapsules, liposomes, chylomicrons, macroparticles, microparticles, nanoparticles, microsponges, or
A cosmetic or dermatological composition characterized by being adsorbed by powdered organic polymer, talc, bentonite and other inorganic media. A cosmetic or dermatological composition according to any one of claims 1 to 5,
The composition, emollient lotion, emollient lotion, emollient cream, skin care or hair care milks, skin care or hair care creams, cleansing lotions, cleansing milk, foundation base, sunscreen lotion, sunscreen lotion, sunscreen cream, self-tanning lotion , self-tanning lotion, self-tanning cream, shaving cream, shaving mousse, aftershave lotions, shampoos, lipsticks, cosmetic or dermopharmaceutical characterized in that it is used by the selected Ru state from the group consisting of mascara or nail varnish Composition. A cosmetic or dermatological composition according to any one of claims 1 to 6,
Wherein in the composition, on one or more, it is added materials commonly used contained as cosmetics,
The additive substance is selected from the group consisting of mixtures that can be used as cosmetics,
The group includes organic solvents or hydroglycol solvents, extraction or synthetic fats, ionic or nonionic thickeners, softeners, turbidity agents, stabilizers, softeners, silicon, α-hydroxy acids, non-foaming agents, perfumes, A cosmetic or dermatological composition comprising a humectant, a chelating agent, a colorant, a gelling and thickening polymer, a surfactant and an emulsifier.